Publications by authors named "Marli Cardoso Martins-Pinge"

29 Publications

  • Page 1 of 1

Swimming training reduces iNOS expression, augments the antioxidant defense and reduces sympathetic responsiveness in the rostral ventrolateral medulla of normotensive male rats.

Brain Res Bull 2021 May 23;170:225-233. Epub 2021 Feb 23.

Departament of Physiological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, PR, Brazil. Electronic address:

We sought to investigate whether RVLM iNOS activity and oxidative profile may participate in the reduction of sympathetic responsiveness in swimming trained normotensive rats. Sedentary (S) and swimming trained (T) Wistar male rats chronically instrumented with an arterial catheter and guide cannula into the RVLM were submitted to continuous pressure and heart rate (HR) recordings and determination of autonomic control (power spectral analysis) before and after unilateral RVLM iNOS inhibition (aminoguanidine, 250 pmol/100 nL). Other S and T rats received local l-glutamate microinjection (5 nmol/100 nL). In separate S and T groups not submitted to brainstem cannulation, fresh bilateral RVLM punchs were collected for iNOS gene expression (qPCR); reduced glutathione and lipid peroxidation quantification (spectrophotometry); iron-reducing antioxidant (FRAP) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) radical cation (ABTS˙) scavenger assays. iNOS gene expression was confirmed in fixed RVLM slices (immunofluorescence). T rats exhibited resting bradycardia, lower sympathovagal balance, reduced RVLM iNOS gene/protein expression and higher antioxidant capacity. Decreased iNOS expression was positively correlated with reduced HR. Pressor and tachycardic response to l-Glutamate were smaller in T rats. Aminoguanidine microinjection reduced sympathetic activity in S rats but did not change it in T rats expressing reduced RVLM iNOS content. Our data indicate that iNOS, expressed in the RVLM of normotensive male rats, has tonic effects on sympathetic activity and that swimming training is an efficient tool to reduce iNOS expression and augment the antioxidant defense, thus reducing glutamatergic responsiveness and sympathetic drive to cardiovascular effectors.
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http://dx.doi.org/10.1016/j.brainresbull.2021.02.023DOI Listing
May 2021

Cardiovascular evaluation of female rats with 6-OHDA-induced parkinsonism: Possible protection by ovarian hormones and participation of nitric oxide.

Life Sci 2020 Oct 12;259:118259. Epub 2020 Aug 12.

Department of Physiological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, PR, Brazil. Electronic address:

Aims: Parkinson's disease (PD) is a neurological disorder caused by environmental and genetic factors, characterized by the death of dopaminergic neurons of the substantia nigra pars compacta (SNpc), leading to a decrease of dopamine in the striatum. In addition to motor symptoms, PD has several abnormalities, among which are cardiovascular changes, such as orthostatic and postprandial hypotension, and blood pressure lability. Studies demonstrate gender differences in PD pathogenesis, indicating that female hormones have a protective role against disease development. However, no studies examining cardiovascular changes in a female rat model of parkinsonism exist.

Main Methods: Wistar female rats were subjected to ovariectomy (OVX) or sham surgery. After seven days, these animals were subjected to bilateral infusion of 6-hydroxydopamine (6-OHDA) or vehicle solution in their SNpc. On the 14th experimental day, a femoral artery catheterization was performed to record cardiovascular parameters after 24 h in conscious state. Analyses of cardiovascular variability and spontaneous baroreflex were performed. The nitrite (NO) concentration in the heart, thoracic aorta, abdominal aorta, and plasma was measured.

Key Findings: The sham-6-OHDA group had no decrease in the mean arterial pressure compared to sham-saline group, whereas the OVX-6-OHDA group presented a baseline decrease in comparison to sham-6-OHDA. The OVX-6-OHDA group showed an NO increase in the heart and abdominal aorta, whereas the sham-6-OHDA group did not. The very low frequency variability component decreased in the sham-6-OHDA but not in the OVX-6-OHDA group.

Significance: We suggest a cardiovascular protection by ovarian hormones in PD with a possible NO involvement.
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http://dx.doi.org/10.1016/j.lfs.2020.118259DOI Listing
October 2020

Concanavalin-A stimulates IL-17 and nitric oxide production and induces macrophage polarization and resistance to Trypanosoma cruzi infection.

Life Sci 2020 Oct 24;258:118137. Epub 2020 Jul 24.

Departamento de Ciências Patológicas, Universidade Estadual de Londrina, Paraná, Brazil. Electronic address:

Aims: Chagas disease is a neglected tropical disease. The ability of Trypanosoma cruzi to survive within phagocytes is likely a critical factor for T. cruzi dissemination in the host. For control of the parasite load and host survival, macrophage action is required. Concanavalin-A (Con-A) presents properties that modulate immune functions and protect hosts from several experimental infectious diseases. Here, we evaluated the effects of Con-A on peritoneal macrophages as well as on the course of experimental infection by T. cruzi.

Main Methods: BALB/c mice, a susceptible model for T. cruzi infection, were treated with Con-A via the intraperitoneal route and 3 days later infected with T. cruzi. We quantified parasitemia, cytokines and nitric oxide (NO). Peritoneal exudate and macrophages were collected for macrophage phenotyping and cell viability, NO and cytokine detection, as well as for T. cruzi internalization and release index determination.

Key Findings: Con-A treatment induced IL-17a and NO production by cells from the peritoneal cavity, and M1 marker expression predominated on peritoneal macrophages. These cells are also more prone to producing TNF-α, IL-6 and NO when infected by T. cruzi and show high trypanocidal capacity. Due to a hostile peritoneal microenvironment caused by Con-A, which induces macrophage cNOS and iNOS expression, infected BALB/c mice showed reduced parasitemia and an increased survival rate.

Significance: We conclude that Con-A can induce peritoneal M1 macrophage polarization to increase trypanocidal activity, resulting in ameliorated systemic infection in a susceptible experimental model.
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http://dx.doi.org/10.1016/j.lfs.2020.118137DOI Listing
October 2020

Combination Therapy Using Benznidazole and Aspirin during the Acute Phase of Experimental Chagas Disease Prevents Cardiovascular Dysfunction and Decreases Typical Cardiac Lesions in the Chronic Phase.

Antimicrob Agents Chemother 2020 06 23;64(7). Epub 2020 Jun 23.

Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná, Brazil

Chagas disease, caused by the protozoan , is one of the main causes of death due to cardiomyopathy and heart failure in Latin American countries. The treatment of Chagas disease is directed at eliminating the parasite, decreasing the probability of cardiomyopathy and disrupting the disease transmission cycle. Benznidazole (BZ) and nifurtimox (Nfx) are recognized as effective drugs for the treatment of Chagas disease by the World Health Organization, but both have high toxicity and limited efficacy, especially in the chronic disease phase. At low doses, aspirin (ASA) has been reported to protect against infection. We evaluated the effectiveness of BZ in combination with ASA at low doses during the acute disease phase and evaluated cardiovascular aspects and cardiac lesions in the chronic phase. ASA treatment prevented the cardiovascular dysfunction (hypertension and tachycardia) and typical cardiac lesions. Moreover, BZ+ASA-treated mice had a smaller cardiac fibrotic area than BZ-treated mice. These results were associated with an increase in numbers of eosinophils and reticulocytes and levels of nitric oxide in the plasma and cardiac tissue of ASA-treated mice relative to respective controls. These effects of ASA and BZ+ASA in chronically infected mice were inhibited by pretreatment with the lipoxin A (LXA) receptor antagonist Boc-2, indicating that the protective effects of ASA are mediated by ASA-triggered lipoxin. These results emphasize the importance of exploring new drug combinations for treatments of the acute phase of Chagas disease that are beneficial for patients with chronic disease.
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http://dx.doi.org/10.1128/AAC.00069-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318042PMC
June 2020

Metabolic syndrome agravates cardiovascular, oxidative and inflammatory dysfunction during the acute phase of Trypanosoma cruzi infection in mice.

Sci Rep 2019 12 11;9(1):18885. Epub 2019 Dec 11.

Department of Physiological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, PR, Brazil.

We evaluated the influence of metabolic syndrome (MS) on acute Trypanosoma cruzi infection. Obese Swiss mice, 70 days of age, were subjected to intraperitoneal infection with 5 × 10 trypomastigotes of the Y strain. Cardiovascular, oxidative, inflammatory, and metabolic parameters were evaluated in infected and non-infected mice. We observed higher parasitaemia in the infected obese group (IOG) than in the infected control group (ICG) 13 and 15 days post-infection. All IOG animals died by 19 days post-infection (dpi), whereas 87.5% of the ICG survived to 30 days. Increased plasma nitrite levels in adipose tissue and the aorta were observed in the IOG. Higher INF- and MCP-1 concentrations and lower IL-10 concentrations were observed in the IOG compared to those in the ICG. Decreased insulin sensitivity was observed in obese animals, which was accentuated after infection. Higher parasitic loads were found in adipose and hepatic tissue, and increases in oxidative stress in cardiac, hepatic, and adipose tissues were characteristics of the IOG group. Thus, MS exacerbates experimental Chagas disease, resulting in greater damage and decreased survival in infected animals, and might be a warning sign that MS can influence other pathologies.
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http://dx.doi.org/10.1038/s41598-019-55363-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906468PMC
December 2019

Differences in cNOS/iNOS Activity during Resistance to Trypanosoma cruzi Infection in 5-Lipoxygenase Knockout Mice.

Mediators Inflamm 2019 24;2019:5091630. Epub 2019 Oct 24.

Laboratório de Imunopatologia Experimental, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, 86051-970 Paraná, Brazil.

Infection with the protozoan causes Chagas disease and consequently leads to severe inflammatory heart condition; however, the mechanisms driving this inflammatory response have not been completely elucidated. Nitric oxide (NO) is a key mediator of parasite killing in -infected mice, and previous studies have suggested that leukotrienes (LTs) essentially regulate the NO activity in the heart. We used infected 5-lipoxygenase-deficient mice (5-LO) to explore the participation of nitric oxide synthase isoforms, inducible (iNOS) and constitutive (cNOS), in heart injury, cytokine profile, and oxidative stress during the early stage of infection. Our evidence suggests that the cNOS of the host is involved in the resistance of 5-LO mice during infection. iNOS inhibition generated a remarkable increase in infection in the blood and heart of mice, whereas cNOS inhibition reduced cardiac parasitism (amastigote nests). Furthermore, this inhibition associates with a higher IFN- production and lower lipid peroxidation status. These data provide a better understanding about the influence of NO-interfering therapies for the inflammatory response toward infection.
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http://dx.doi.org/10.1155/2019/5091630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854994PMC
May 2020

Glutamate and GABA neurotransmission are increased in paraventricular nucleus of hypothalamus in rats induced to 6-OHDA parkinsonism: Involvement of nNOS.

Acta Physiol (Oxf) 2019 07 27;226(3):e13264. Epub 2019 Feb 27.

Departament of Physiological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, Brazil.

Aim: Parkinson's disease (PD) is a progressive neurodegenerative disease that manifests itself clinically after reaching an advanced pathological stage. Besides motor signals, PD patients present cardiovascular and autonomic alterations. Recent data showed that rats induced to Parkinsonism by 6-hydroxydopamine (6-OHDA) administration in the substantia nigra pars compacta (SNpc) showed lower mean arterial pressure (MAP) and heart rate (HR), as reduction in sympathetic modulation. The paraventricular nucleus of the hypothalamus (PVN) is an important site for autonomic and cardiovascular control, and amino acid neurotransmission has a central role. We evaluate PVN amino acid neurotransmission in cardiovascular and autonomic effects of 6-OHDA Parkinsonism.

Methods: Male Wistar rats were submitted to guide cannulas implantation into the PVN. 6-OHDA or sterile saline (sham) was administered bilaterally in the SNpc. After 7 days, cardiovascular recordings in conscious state was performed.

Results: Bicuculline promoted an increase in MAP and HR in sham group and exacerbated those effects in 6-OHDA group. NBQX (non-NMDA inhibitor) did not promote changes in sham as in 6-OHDA group. On the other hand, PVN microinjection of LY235959 (NMDA inhibitor) in sham group did not induced cardiovascular alterations, but decreased MAP and HR in 6-OHDA group. Compared to Sham group, 6-OHDA lesion increased the number of neuronal nitric oxide synthase (nNOS)-immunoreactive neurons in the PVN and, nNOS inhibition promoted higher increases in MAP and HR.

Conclusion: Our data suggest that the decreased baseline blood pressure and heart rate in animals with Parkinsonism may be due to an increased GABAergic tone via nNOS in the PVN.
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http://dx.doi.org/10.1111/apha.13264DOI Listing
July 2019

The essential role of hypothalamic paraventricular nucleus nNOS in the modulation of autonomic control in exercised rats.

Nitric Oxide 2018 09 3;79:14-24. Epub 2018 Jul 3.

Departament of Physiological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, PR, Brazil. Electronic address:

Nitric oxide (NO), an intercellular signaling molecule is relevant for circulatory autonomic control. Brain NO synthase (NOS) and NO levels were downregulated in pathological conditions, but rescued after exercise training. We hypothesized that exercise training was also able to improve NO modulation within the hypothalamic paraventricular nucleus (PVN) of healthy rats. Male Wistar rats were submitted to two 4-weeks protocols: i) swimming training (T) or kept sedentary (S), ii) l-arginine (62,5 mg/mL, 1 mL/day p. o.) or vehicle supplementation. Rats underwent stereotaxic surgery (PVN bilateral guide cannulas) and chronic catheterization of artery/vein. Arterial pressure (AP), heart rate (HR) and baroreflex sensitivity were recorded in conscious rats at rest and following a selective nNOS inhibitor (Nw-Propyl-l-Arginine, 4 nmol/100 nL) within the PVN. Rats were deeply anesthetized for brain perfusion/harvesting after respiratory arrest. In separate groups (T and S, l-arginine and Vehicle supplemented) not submitted to PVN cannulation, fresh and fixed brains were obtained for gene and protein nNOS expression (qPCR and immunohistochemistry) and nitrite levels (Griess reaction). T and l-arginine treatment were accompanied by resting bradycardia, augmented parasympathetic and reduced sympathetic activity to heart and vessels (power spectral analysis) and increased baroreflex sensitivity (P < 0.05). In contrast, PVN nNOS inhibition blocked/attenuated these effects in addition to significantly increase in resting MAP and HR (with larger effects in T and l-arginine treated rats vs. respective controls, P < 0.05). T increased nNOS gene and protein expression within the ventromedial and posterior PVN nuclei (P < 0.05). PVN nitirite levels were also increased in T and l-arginine groups (P < 0.05). Data strongly suggest that training by increasing NO availability within PVN preautonomic nuclei favors both the slow down of sympathetic and the augmentation of parasympathetic activity and facilitates baroreflex control, therefore improving autonomic regulation of the heart in healthy rats.
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http://dx.doi.org/10.1016/j.niox.2018.07.002DOI Listing
September 2018

Nitric oxide alterations in cardiovascular system of rats with Parkinsonism induced by 6-OHDA and submitted to previous exercise.

Life Sci 2018 Jul 7;204:78-86. Epub 2018 May 7.

Departamento de Ciências Fisiológicas, Universidade Estadual de Londrina - UEL, Londrina, PR, Brazil. Electronic address:

Studies showed that physical exercise decreases the risk of developing Parkinson's disease (PD) as slowing its progression. Nitric oxide (NO) increases in the substantia nigra pars compacta (SNpc) of individuals with PD. However, no study has evaluated the effects of exercise on peripheral NO levels and its modulatory effects on cardiovascular dysfunctions of subjects with PD. Trained (T) or sedentary (S) animals underwent stereotactic surgery for bilateral 6-hydroxydopamine (6-OHDA) or vehicle microinfusion (Sham group). After 6 days, the animals were catheterized for baseline parameters, followed by inhibition of NOS by Nw-nitro-arginine-methyl ester (L-NAME, 10 mg/kg - i.v.). Nitrite concentration was performed in the aorta, heart, kidney, adrenal and plasma. After exercise, the animals presented resting bradycardia (6-OHDA T and Sham T). NO was increased in the aorta of 6-OHDA S, and decreased in 6-OHDA T animals. In the heart, NO was increased in Sham T compared to sedentary and decreased in 6-OHDA T relative to 6-OHDA S and Sham T animals. At the kidney, NO decrease in 6-OHDA S and Sham T when compared to Sham S and, in adrenal gland, there was a decrease in 6-OHDA T in relation to 6-OHDA S. L-NAME promoted lower increases in MAP in 6-OHDA groups. The decreases of HR were enhanced due to physical training. 6-OHDA S group presented decreased systolic arterial pressure variability, not altered by exercise. Our data showed alterations in peripheral NO in the association of exercise with Parkinsonism in the cardiovascular function.
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http://dx.doi.org/10.1016/j.lfs.2018.05.017DOI Listing
July 2018

iNOS inhibition improves autonomic dysfunction and oxidative status in hypertensive obese rats.

Clin Exp Hypertens 2017 5;39(1):50-57. Epub 2017 Jan 5.

a Department of Physiological Sciences , State University of Londrina , Londrina , Brazil.

It has been suggested that nitric oxide (NO) from iNOS source is involved in inflammation and oxidative stress, and hypertension in obese subjects involves an inflammatory process. However, no study evaluated the participation of iNOS inhibition on cardiovascular, autonomic, and inflammatory parameters in obese rats. Obesity was induced by the administration of 4 mg/g body weight of monosodium glutamate (MSG) or equimolar saline (CTR) in newborn rats. On the 60th day, treatment with aminoguanidine (Amino, 50 mg/kg), an iNOS inhibitor, or 0.9% saline, was started. On the 90th day, mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious rats and autonomic modulation was conducted with the CardioSeries software. Plasma samples were collected to assess lipid peroxidation and prostaglandins (PGE). In addition, iNOS immunohistochemistry in cardiac tissue was evaluated. MSG rats showed hypertension compared to CTR, and Amino treatment did not reverse it. Obese rats presented increased sympathetic and decreased parasympathetic modulation to the heart, reverted by Amino treatment. Plasma PGE was increased in obese rats, and Amino treatment decreased. Obese rats presented increased plasma lipoperoxidation, which was decreased after Amino treatment. Also, cardiac iNOS immunohistochemistry was decreased after Amino treatment. Our data suggest that iNOS activation is involved in the systemic and cardiac mechanisms of oxidative stress, inflammation, and autonomic dysfunction derived from obesity.
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http://dx.doi.org/10.1080/10641963.2016.1210628DOI Listing
February 2017

Chemoreflex and baroreflex alterations in Parkinsonism induced by 6-OHDA in unanesthetized rats.

Neurosci Lett 2015 Oct 25;607:77-82. Epub 2015 Sep 25.

Department of Physiological Sciences, State University of Londrina, Londrina, PR, Brazil. Electronic address:

Parkinson's disease (PD) is mainly characterized by motor signals. However, non-motor signals also affect and decrease the quality of life of PD patients. Among these non-motor signs are cardiovascular disorders as orthostatic hypotension, postprandial hypotension and cardiac arrhythmias, which may be due to the involvement of both central nervous system and peripheral autonomic nervous system. In the present study we investigated the cardiovascular function, evaluating cardiovascular reflexes (chemoreflex and baroreflex), in an animal model of Parkinsonism induced by bilateral infusion of the toxin 6-hydroxydopamine (6-OHDA), in the substantia nigra pars compacta (SNpc). The results showed that the animals induced to Parkinsonism had lower arterial pressure (AP) and heart rate HR) compared to control animals. We showed that after activation of the baroreceptors by phenylephrine (Phe) and sodium nitroprusside (SNP), the baroreflex sensitivity index was not changed between the groups. However, there was a greater increase in the AP when stimulated with Phe and greater tachycardia when stimulated with SNP in 6-OHDA animals. After activation of the peripheral chemoreceptors through KCN injection (cytotoxic hypoxia), there was a higher increase in pressor and bradycardic response in injured animals with bilateral 6-OHDA. These changes in the cardiovascular reflexes may be important adjustments mechanisms to maintain the cerebral blood flow in those animals, and may be a result of denervation supersensitivity to catecholamines in autonomic targets.
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http://dx.doi.org/10.1016/j.neulet.2015.09.024DOI Listing
October 2015

Splenectomy attenuates obesity and decreases insulin hypersecretion in hypothalamic obese rats.

Metabolism 2015 Sep 7;64(9):1122-33. Epub 2015 May 7.

Department of General Biology, State University of Ponta Grossa, Ponta Grossa, Parana, Brazil.

Objective: Obesity-induced abnormalities, such as insulin resistance, dyslipidemia and hypertension, are frequently correlated with low-grade inflammation, a process that may depend on normal spleen function. This study investigated the role of the spleen in the obesity induced by monosodium glutamate (MSG) treatment.

Materials/methods: MSG-obese and lean control (CON) rats were subjected to splenectomy (SPL) or non-operated (NO).

Results: MSG-NO rats presented a high adipose tissue content, insulin resistance, dyslipidemia and islet hypersecretion, accompanied by hypertrophy of both pancreatic islets and adipocytes when compared with CON-NO rats. In addition, changes in nitric oxide response were found in islets from the MSG-NO group without associated alterations in inducible nitric oxide synthase (iNOS) or IL1β expression. MSG-NO also presented increased leukocyte counts and augmented LPS-induced nitric oxide production in macrophages. Splenectomy of MSG-obese animals decreased insulin hypersecretion, normalized the nitric oxide response in the pancreatic islets, improved insulin sensitivity and reduced hypertrophy of both adipocytes and islets, when compared with MSG-NO rats.

Conclusion: Results show that splenectomy attenuates the progression of the obesity modulating pancreas functions in MSG-obese rats.
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http://dx.doi.org/10.1016/j.metabol.2015.05.003DOI Listing
September 2015

Functional evidence of paraventricular nucleus involvement in cardiovascular and autonomic modulation in response to acute microgravity (head-down tilt) in unanesthetized rats.

J Neurosci Res 2015 Aug 28;93(8):1305-12. Epub 2015 Mar 28.

Department of Physiological Sciences, State University of Londrina, Londrina, Paraná Region, Brazil.

Exposure to microgravity induces autonomic and vestibular disorders such as alterations in cardiovascular function. The paraventricular nucleus of the hypothalamus (PVN) is known to be an important center for integrating autonomic and cardiovascular responses as blood volume reflexes. The acute effects promoted by microgravity and PVN involvement in cardiovascular and autonomic parameters have not yet been evaluated. Male Wistar rats were anesthetized to facilitate cannulae implantation in the PVN. After 3 days of surgical recovery, femoral artery and vein catheters were implanted for direct recording of blood pressure and heart rate (HR) in conscious animals to evaluate cardiovascular and autonomic changes in an acute protocol of head-down tilt (HDT) in nonanesthetized rats. During HDT, there was an increase in mean arterial pressure (11 ± 1 mmHg, P < 0.05) and a decrease in HR (-28 ± 5 bpm, P < 0.05). Spectral analysis of systolic arterial pressure showed an increase in the low-frequency (LF) component. In addition, HDT induced a reduction in the LF component and an increase in the high-frequency (HF) component of the pulse interval (PI). PVN inhibition with muscimol reversed bradycardia and blocked the reduction of the LF and HF increases in PI during HDT. These results suggest that the PVN participates in the cardiovascular compensation during HDT, especially modulating cardiac responses.
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http://dx.doi.org/10.1002/jnr.23586DOI Listing
August 2015

Nitric oxide-releasing indomethacin enhances susceptibility to Trypanosoma cruzi infection acting in the cell invasion and oxidative stress associated with anemia.

Chem Biol Interact 2015 Feb 2;227:104-11. Epub 2015 Jan 2.

Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86051-970 Londrina, Paraná, Brazil. Electronic address:

Trypanosoma cruzi is the causative agent of Chagas disease. Approximately 8 million people are thought to be affected with this disease worldwide. T. cruzi infection causes an intense inflammatory response, which is critical for the control of parasite proliferation and disease development. Nitric oxide-donating nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are an emergent class of pharmaceutical derivatives with promising utility as chemopreventive agents. In this study, we investigated the effect of NO-indomethacin on parasite burden, cell invasion, and oxidative stress in erythrocytes during the acute phase of infection. NO-indomethacin was dissolved in dimethyl formamide followed by i.p. administration of 50 ppm into mice 30 min after infection with 5×10(3) blood trypomastigote forms (Y strain). The drug was administered every day until the animals died. Control animals received 100 μL of drug vehicle via the same route. Within the NO-indomethacin-treatment group, parasitemia and mortality (100%) were higher and oxidative stress in erythrocytes, anemia, and entry of parasites into macrophages were significantly greater than that seen in controls. Increase in the entry and survival of intracellular T. cruzi was associated with inhibition of nitric oxide production by macrophages treated with NO-indomethacin (2.5 μM). The results of this study provide strong evidence that NO-NSAIDs potently inhibit nitric oxide production, suggesting that NO-NSAID-based therapies against infections would be difficult to design and would require caution.
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http://dx.doi.org/10.1016/j.cbi.2014.12.024DOI Listing
February 2015

Direct renin inhibitor therapy and swimming training: hemodynamic and cardiac effects in hypertensive and normotensive rats.

Clin Exp Hypertens 2015 27;37(4):345-52. Epub 2014 Oct 27.

Department of Physical Education, Physical Education and Sports Center, State University of Londrina , Londrina-PR , Brazil .

Purpose: This study aimed to analyze the hemodynamic and cardiac effects of direct renin inhibitor (DRI) treatment and swimming training in hypertensive rats.

Methods: Seventy-seven rats were divide into eight groups: sedentary normotensive (SN), trained normotensive (TN), sedentary normotensive treated with DRI (SN_DRI), trained normotensive treated with DRI (TN_DRI), sedentary hypertensive (SH), trained hypertensive (TH), sedentary hypertensive treated with DRI (SH_DRI), trained hypertensive treated with DRI (TH_DRI). Swimming training occurred for up to 60 min, five times a week for four weeks. The hypertensive animals were treated with 20 mg ċ kg(-1) ċ day(-1) L-NAME for four weeks. Groups treated with DRI received 10 mg ċ kg(-1) ċ day(-1) of aliskiren for four weeks. After the treatment period, all the animals underwent femoral artery catheterization surgery for direct measurement of cardiovascular variables.

Results: The SH group presented hypertension (136.4 ± 5.0 mmHg) compared to the SN (107.1 ± 1.7 mmHg). The TH group showed lower mean arterial pressure (MAP) than the SH (121.1 ± 1.3 mmHg), but the treatment with DRI did not attenuate hypertension (128.2 ± 4.9 mmHg). The analysis of collagen areas demonstrated that treatment with DRI may attenuate cardiac remodeling in situations of hypertension, in the condition of treatment alone or combined with physical training.

Conclusion: Both interventions in combination may be more effective at reducing cardiovascular risk in hypertensive subjects.
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http://dx.doi.org/10.3109/10641963.2014.972562DOI Listing
August 2016

Aspirin modulates innate inflammatory response and inhibits the entry of Trypanosoma cruzi in mouse peritoneal macrophages.

Mediators Inflamm 2014 19;2014:580919. Epub 2014 Jun 19.

Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86057-970 Londrina, PR, Brazil.

The intracellular protozoan parasite Trypanosoma cruzi causes Chagas disease, a serious disorder that affects millions of people in Latin America. Cell invasion by T. cruzi and its intracellular replication are essential to the parasite's life cycle and for the development of Chagas disease. Here, we present evidence suggesting the involvement of the host's cyclooxygenase (COX) enzyme during T. cruzi invasion. Pharmacological antagonist for COX-1, aspirin (ASA), caused marked inhibition of T. cruzi infection when peritoneal macrophages were pretreated with ASA for 30 min at 37°C before inoculation. This inhibition was associated with increased production of IL-1β and nitric oxide (NO(∙)) by macrophages. The treatment of macrophages with either NOS inhibitors or prostaglandin E2 (PGE2) restored the invasive action of T. cruzi in macrophages previously treated with ASA. Lipoxin ALX-receptor antagonist Boc2 reversed the inhibitory effect of ASA on trypomastigote invasion. Our results indicate that PGE2, NO(∙), and lipoxins are involved in the regulation of anti-T. cruzi activity by macrophages, providing a better understanding of the role of prostaglandins in innate inflammatory response to T. cruzi infection as well as adding a new perspective to specific immune interventions.
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http://dx.doi.org/10.1155/2014/580919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089847PMC
February 2015

Systemic toxicity induced by paclitaxel in vivo is associated with the solvent cremophor EL through oxidative stress-driven mechanisms.

Food Chem Toxicol 2014 Jun 19;68:78-86. Epub 2014 Mar 19.

Laboratory of Physiopathology and Free Radicals, Department of Pathology, State University of Londrina, Londrina, Paraná, Brazil.

The toxic effects of paclitaxel (PTX) and its solubilizing agent cremophor EL (CREL) have been well established in vitro; however, the in vivo mechanisms underlying this toxicity remain unclear. Thus, the aim of this study was to analyze the in vivo toxicity induced by infusion of PTX and CREL and to investigate the involvement of oxidative stress as a potential mechanism for this toxicity. We treated male Wistar rats with PTX and/or CREL for 1h using human-equivalent doses (PTX+CREL/ethanol+NaCl 175mg/m(2) or CREL+ethanol+NaCl) and sacrificed immediately or 24h after these drug infusions to systemic biochemical evaluations. Hidrosoluble vitamin E (vitE, Trolox) was added as a control in some groups. The oxidative profile was determined by measuring erythrocyte and plasma lipid peroxidation, superoxide dismutase and catalase activities, reduced glutathione (GSH) levels, red blood cell (RBC) counts, hemoglobin profile, plasma total radical-trapping antioxidant parameter (TRAP), plasma lipid peroxidation, nitric oxide levels and malondialdehyde levels. Our findings showed that CREL infusion triggered immediate high plasma lipid peroxidation and augmented TRAP, while PTX caused immediate TRAP consumption and metahemoglobin formation. Pronounced oxidative effects were detected 24h after infusion, when CREL treatment enhanced RBC counts and plasma lipid peroxidation, increased catalase activity, and decreased TRAP levels. On the other hand, after 24h, PTX-infused rats showed reduced catalase activity and reduced metahemoglobin levels. These data indicate the existence of a continuous oxidative stress generation during CREL-PTX treatment and highlight CREL as primarily responsible for the in vivo oxidative damage to RBCs.
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http://dx.doi.org/10.1016/j.fct.2014.03.013DOI Listing
June 2014

Decreased endothelial nitric oxide, systemic oxidative stress, and increased sympathetic modulation contribute to hypertension in obese rats.

Am J Physiol Heart Circ Physiol 2014 May 14;306(10):H1472-80. Epub 2014 Mar 14.

Department of Physiological Sciences State University of Londrina, Londrina, PR;

We investigated the involvement of nitric oxide (NO) and reactive oxygen species (ROS) on autonomic cardiovascular parameters, vascular reactivity, and endothelial cells isolated from aorta of monosodium glutamate (MSG) obese rats. Obesity was induced by administration of 4 mg/g body wt of MSG or equimolar saline [control (CTR)] to newborn rats. At the 60th day, the treatment was started with N(G)-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg) or 0.9% saline. At the 90th day, after artery catheterization, mean arterial pressure (MAP) and heart rate were recorded. Plasma was collected to assess lipid peroxidation. Endothelial cells isolated from aorta were evaluated by flow cytometry and fluorescence intensity (FI) emitted by NO-sensitive dye [4,5-diaminofluoresceindiacetate (DAF-2DA)] and by ROS-sensitive dye [dihydroethidium (DHE)]. Vascular reactivity was made by concentration-response curves of acetylcholine. MSG showed hypertension compared with CTR. Treatment with L-NAME increased MAP only in CTR. The MSG induced an increase in the low-frequency (LF) band and a decrease in the high-frequency band of pulse interval. L-NAME treatment increased the LF band of systolic arterial pressure only in CTR without changes in MSG. Lipid peroxidation levels were higher in MSG and were attenuated after L-NAME. In endothelial cells, basal FI to DAF was higher in CTR than in MSG. In both groups, acetylcholine increased FI for DAF from basal. The FI baseline to DHE was higher in MSG than in CTR. Acetylcholine increased FI to DHE in the CTR group, but decreased in MSG animals. We suggest that reduced NO production and increased production of ROS may contribute to hypertension in obese MSG animals.
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http://dx.doi.org/10.1152/ajpheart.00520.2013DOI Listing
May 2014

Paraventricular nucleus of hypothalamus participates in the sympathetic modulation and spontaneous fluctuation of baroreflex during head up tilt in unanesthetized rats.

Neurosci Lett 2014 Jan 28;558:1-7. Epub 2013 Oct 28.

Department of Physiological Sciences, State University of Londrina, Londrina, PR, Brazil. Electronic address:

The autonomic nervous system is importantly involved in the maintenance of arterial pressure during orthostatic challenges. However, little is known about the specific central areas involved in these cardiovascular compensations. It has been proposed that the paraventricular nucleus of the hypothalamus (PVN) is involved in cardiovascular reflex responses related to blood volume. Our hypothesis is that PVN is involved in autonomic modulation during an orthostatic challenge (head up tilt, HUT). Adult male Wistar rats, instrumented with guide cannulas to the PVN and femoral artery and vein catheters were submitted to mean arterial pressure (MAP) and heart rate (HR) recordings in conscious state. After baseline parameters the rats were submitted to HUT. The spectral analysis during HUT showed an increase in low-frequency oscillation of systolic arterial pressure (SAP) (LF: 14.21±2.73-32.44±8.43 mmHg(2)) and pulse interval (PI) (LF: 14.05±4.25-51.79±10.64 n.u.) and a decrease in high-frequency oscillation (HF; 84.52±4.82-47.49±10.30 n.u.). Previous bilaterally microinjection of cobalt chloride (1 mM/100 nl), a calcium channel blocking agent, into the PVN decreased LF oscillations of SAP (LF: 32.44±8.43-13.23±1.87 mmHg(2)) as well as in PI (LF: 12.38±3.76-5.03±1.20 ms(2)). Muscimol microinjection (40 mM), a GABAA agonist, decreased LF component of PI oscillations (LF: 51.79±10.64-25.76±5.34 n.u.). The baroreflex gain was not altered by HUT, but during tilt, with PVN previously inhibited by muscimol or cobalt chloride, the gain was reduced. Our data suggest that the PVN participates in the brain circuitry involved in autonomic adjustment during orthostatic challenges.
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http://dx.doi.org/10.1016/j.neulet.2013.09.039DOI Listing
January 2014

Glutamatergic neurotransmission in the hypothalamus PVN on heart rate variability in exercise trained rats.

Auton Neurosci 2012 Sep;170(1-2):42-7

Department of Physiological Sciences, Center of Biological Sciences, State University of Londrina, PR, Brazil.

The paraventricular nucleus of hypothalamus (PVN) is a well known site of integration for autonomic and cardiovascular responses, and the glutamate neurotransmitter plays an important role. The aim of our study was to evaluate the cardiovascular parameters and autonomic modulation by means of spectral analysis after ionotropic glutamate receptor inhibition in the PVN in conscious sedentary (S) or swimming trained (ST) rats. After exercise training protocol, adult male Wistar rats, instrumented with guide cannulae to PVN and artery and vein catheters were submitted to mean arterial pressure (MAP) and heart rate (HR) recording. At baseline, physical training induced a resting bradycardia (S: 379 ± 3, ST: 349 ± 2 bpm, Pb<0.05) and promoted adaptations in HRV characterized by an increase of HF in normalized values and a decrease of LF in absolute and normalized units compared with the sedentary group. Microinjection of kynurenic acid (KYNA) in the PVN of sedentary and trained rats promoted decreases in MAP and HR, but the decrease in HR was smaller in the trained animals (ΔHRS: -48 ± 7, ST: -28 ± 4 bpm, Pb<0.05). Furthermore, the differences in baseline parameters of pulse interval, found between sedentary and trained animals, disappeared after KYNA microinjection in the PVN. Our data suggest that the cardiovascular and autonomic adaptations to the heart induced by exercise training may involve glutamatergic mechanisms in the PVN.
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http://dx.doi.org/10.1016/j.autneu.2012.07.007DOI Listing
September 2012

Renal sympathetic nerve activity is increased in monosodium glutamate induced hyperadipose rats.

Neurosci Lett 2012 Aug 15;522(2):118-22. Epub 2012 Jun 15.

Department of Physiological Sciences, State University of Londrina, Londrina, PR, Brazil.

The literature suggests that both obesity and hypertension are associated with increased sympathetic nerve activity. In the present study we evaluated the renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) in hyperadipose rats induced by neonatal administration of monosodium glutamate (MSG). Neonatal Wistar male rats were injected with MSG (4 mg/g body weight ID) or equimolar saline (control) for 5 days. At 90th day, all rats were anesthetized (urethane 1.4 g/kg) and prepared for MAP, HR and renal sympathetic nerve activity recordings. The anesthetized MSG rats presented baseline hypertension and increased baseline RSNA compared with control. Our results suggest the involvement of the renal sympathetic nervous system in the physiopathology of the MSG obesity.
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http://dx.doi.org/10.1016/j.neulet.2012.06.021DOI Listing
August 2012

Altered baroreflex and autonomic modulation in monosodium glutamate-induced hyperadipose rats.

Metabolism 2012 Oct 1;61(10):1435-42. Epub 2012 May 1.

Department of Physiological Sciences, State University of Londrina, Londrina, PR, Brazil.

We aimed to examine the cardiovascular function by tonic and baroreflex alterations in obese rats induced by monosodium glutamate (MSG). Neonatal male Wistar rats were injected with MSG (4 mg/g body weight) or equimolar saline (control, C). At 90 days, all rats were anesthetized for catheterization of the femoral artery for mean arterial pressure (MAP) and heart rate (HR) recordings in the conscious state. After baseline, we performed IV treatment with hexamethonium (25 mg/kg), or atropine (1 mg/kg) or propranolol (3 mg/kg). We also performed the spectral analysis of heart rate variability (HRV) and baroreflex sensitivity. Baseline comparison showed that obese rats are hypertensive compared with control (C=110±2 mmHg; MSG=: 123±3 mmHg, P<0.05). After ganglionic blockade with hexamethonium the differences in MAP between control and obese rats disappeared. Beta adrenergic blockade with propranolol induced a greater decrease in heart rate compared with control. The analysis of HRV showed that obese rats have increased modulation by both components of the autonomic nervous system compared with control rats. The baroreflex gain showed increased sensitivity for the parasympathetic component in the obese rats (C=-2.41±0.25; MSG=-3.34±0.23 bpm/mmHg) compared with control. Our data suggest that both components of autonomic cardiac tonus and the parasympathetic component of the baroreflex sensitivity are increased in the MSG obese rat. It is possible that the parasympathetic alterations observed in these MSG obese rats may have originated from central areas of cardiovascular control.
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http://dx.doi.org/10.1016/j.metabol.2012.03.005DOI Listing
October 2012

Involvement of the paraventricular nucleus (PVN) of hypothalamus in the cardiovascular alterations to head up tilt in conscious rats.

Neurosci Res 2012 Mar 13;72(3):270-4. Epub 2011 Dec 13.

Department of Physiological Sciences, State University of Londrina, Londrina, PR, Brazil.

We evaluated the involvement of paraventricular nucleus (PVN) in the changes in mean arterial pressure (MAP) and heart rate (HR) during an orthostatic challenge (head up tilt, HUT). Adult male Wistar rats, instrumented with guide cannulas to PVN and artery and vein catheters were submitted to MAP and HR recording in conscious state and induction of HUT. The HUT induced an increase in MAP and HR and the pretreatment with prazosin and atenolol blocked these effects. After inhibition of neurotransmission with cobalt chloride (1 mM/100 nl) into the PVN the HR parameters did not change, however we observed a decrease in MAP during HUT. Our data suggest the involvement of PVN in the brain circuitry involved in cardiovascular adjustment during orthostatic challenges.
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http://dx.doi.org/10.1016/j.neures.2011.12.001DOI Listing
March 2012

COX-2 inhibition does not reverse the increased sympathetic modulation in MSG obese rats.

Auton Neurosci 2011 Dec 6;165(2):201-4. Epub 2011 Aug 6.

Department of Physiological Sciences, State University of Londrina, Londrina, PR, Brazil.

We evaluate the effects of chronic treatment with celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, on blood pressure (BP) and heart rate variability (HRV) in obese rats induced by neonatal monosodium glutamate (MSG). The animals were treated with celecoxib or saline for 30 days (from the 60th to the 90th day of age). On the 90th day, the MSG obesity induced an increase in the low-frequency (LF) component (CTR=5.69±18.30ms(2), MSG=38.49±6.27ms(2)) and a decrease in the high-frequency (HF) component of HRV (CTR=71.48±6.22ms(2), MSG=50.94±7.03ms(2)), which were unchanged by celecoxib treatment. We suggest that HRV in MSG obesity involves a greater sympathetic modulation not related with COX-2 products.
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http://dx.doi.org/10.1016/j.autneu.2011.07.006DOI Listing
December 2011

Nitric oxide inhibition in paraventricular nucleus on cardiovascular and autonomic modulation after exercise training in unanesthetized rats.

Brain Res 2011 Feb 21;1375:68-76. Epub 2010 Dec 21.

Department of Physiological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, Paraná, Brazil.

It is well known that regular physical exercise alter cardiac function and autonomic modulation of heart rate variability (HRV). The paraventricular nucleus of hypothalamus (PVN) is an important site of integration for autonomic and cardiovascular responses, where nitric oxide (NO) plays an important role. The aim of our study was to evaluate the cardiovascular parameters and autonomic modulation by means of spectral analysis after nitric oxide synthase (NOS) inhibition in the PVN in conscious sedentary (S) or swimming trained (ST) rats. After swimming training protocol, adult male Wistar rats, instrumented with guide cannulas to PVN and femoral artery and vein catheters were submitted to mean arterial pressure (MAP) and heart rate (HR) recording. At baseline, the physical training induced a resting bradycardia (S: 374±5, ST: 346±1bpm) and promoted adaptations in HRV characterized by an increase in high-frequency oscillations (HF; 26.43±6.91 to 88.96±2.44) and a decrease in low-frequency oscillations (LF; 73.57±6.91 to 11.04±2.44) in normalized units. The microinjection of N(ω)-nitro-l-arginine methyl ester (l-NAME) in the PVN of sedentary and trained rats promoted increase in MAP and HR. l-NAME in the PVN did not significantly alter the spectral parameters of HRV of sedentary animals, however in the trained rats increased LF oscillations (11.04±2.44 to 27.62±6.97) and decreased HF oscillations (88.96±2.44 to 72.38±6.97) in normalized units compared with baseline. Our results suggest that NO in the PVN may collaborate to cardiac autonomic modulation after exercise training.
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http://dx.doi.org/10.1016/j.brainres.2010.12.049DOI Listing
February 2011

Effects of nitric oxide in mucociliary transport.

Braz J Otorhinolaryngol 2009 Nov-Dec;75(6):866-71

Londrina Federal University.

Unlabelled: The airways are made up of ciliated epithelium which secretes mucous, protecting the respiratory tract from particles inhaled during breathing. Its is paramount to understand the physiology and the mechanisms involved in mucociliary activity. Literature suggests that Nitric oxide (NO), especially the one produced by iNOS expression, maintains the mucociliary function and the immune defense of the nasal cavity.

Aim: to assess NO participation and the enzymatic pathways in the production of NO and mucociliary transport, using constructive and inductive NO synthetase inhibitors, L-NAME and aminoguanidine, respectively.

Materials And Methods: frog palates were prepared and immersed in ringer (control), L-NAME or aminoguanidine solutions. The palates were immersed in these solutions for four periods of 15 minutes. Mucociliary transport measures were carried out before and after each exposure.

Results: control palates maintained stable their transportation speed. L-NAME increased, while aminoguanidine reduced mucous transportation velocity.

Conclusion: unspecific cNOS block with L-NAME and relatively specific iNOS block with aminoguanidine results leads us to propose that depending on the pathway, the NO can increase or reduce mucociliary transport in frog palates.
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http://dx.doi.org/10.1016/s1808-8694(15)30551-6DOI Listing
June 2010

Role of paraventricular nucleus in exercise training-induced autonomic modulation in conscious rats.

Auton Neurosci 2009 Jun 18;148(1-2):28-35. Epub 2009 Mar 18.

Department of Physiological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, PR, Brazil.

The paraventricular nucleus (PVN) of the hypothalamus is an important site for autonomic regulation, where gamma-aminobutyric acid (GABA) system plays an important role. The central mechanisms underlying modulatory effects of exercise training have yet to be characterized. Our objective was to analyze the effects on the autonomic modulation and hemodynamic parameters after bicuculline or muscimol injections into the PVN of sedentary (control, C) and previously submitted to swimming training (ST) rats. After ST protocol, adult male Wistar rats, instrumented with guide cannulas to PVN and femoral artery and vein catheters were submitted to mean arterial pressure (MAP) recording. The exercise training reduced the LF oscillations in normalized units and increased the HF oscillations in absolute and normalized units. Compared with the C group, muscimol microinjections in the ST group promoted a higher decrease in MAP (C=-14+/-1 vs. ST=-28+/-4 mm Hg). Spectral analysis of HR (pulse interval) showed that the muscimol microinjections also reduced LF and HF oscillations in absolute units in both groups. Bicuculline microinjections increased the systolic arterial pressure (C=155+/-5, ST=164+/-5 mm Hg) in ST compared with the C group. Bicuculline injections also increased the LF oscillations of HR in absolute units in C and ST groups. Meanwhile, in normalized units only the ST group showed an increase in the LF oscillations. Our data showed that PVN has an important role in autonomic modulation after exercise training.
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http://dx.doi.org/10.1016/j.autneu.2009.02.007DOI Listing
June 2009

Cardiovascular and pulmonary effects of NOS inhibition in endotoxemic conscious rats subjected to swimming training.

Life Sci 2007 Sep 19;81(16):1301-8. Epub 2007 Sep 19.

Department of Physiological Sciences, State University of Londrina, Campus Universitário, CEP 86055-900 Londrina, PR, Brazil.

Sepsis is characterized by systemic hypotension, hyporeactiveness to vasoconstrictors, impaired tissue perfusion, and multiple organ failure. During exercise training (ET), dynamic cardiovascular adjustments take place to maintain proper blood pressure and adjust blood supply to different vascular beds. The aim of this study was to investigate whether ET protects against the cardiovascular abnormalities induced by LPS, a model of experimental endotoxemia, and to evaluate the role of nitric oxide (NO) in pulmonary edema. Wistar rats were subjected to swimming training (up to 1 h/day, 5 days/week for 4 weeks) after which their femoral artery and vein were catheterized. LPS (5 mg/kg, i.v.), injected in control (C) and trained animals (ET), promoted 3 distinct phases in mean arterial pressure (MAP) and heart rate (HR). After ET the alterations in MAP were attenuated. The ET animals showed a lower pulmonary edema index (PEI) after LPS (C=0.65+/-0.01; ET=0.60+/-0.02), which was attenuated after treatment with aminoguanidine in both groups (C=0.53+/-0.02; ET=0.53+/-0.02, p<0.05). After l-NAME, PEI was enhanced numerically in the C and was statistically higher in the ET group (C=0.73+/-0.05; ET=1.30+/-0.3, p<0.05). 7-nitroindazole did not promote any alteration in either group. The adaptations promoted by ET seem to be beneficial, counteracting the cardiovascular abnormalities and pulmonary edema seen in septicemia induced by LPS. The results suggest that iNOS aggravates and cNOS protects against this pulmonary edema.
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http://dx.doi.org/10.1016/j.lfs.2007.09.006DOI Listing
September 2007

Attenuated pressor responses to amino acids in the rostral ventrolateral medulla after swimming training in conscious rats.

Auton Neurosci 2005 Oct 1;122(1-2):21-8. Epub 2005 Sep 1.

Department of Physiological Sciences, Center of Biological Sciences, State University of Londrina, Londrina, Paraná, Brazil.

The cardiovascular effects of microinjection of the amino acids glutamate and glycine within the rostral ventrolateral medulla (RVLM) after swimming training (ST) in unrestrained awake rats were investigated. Unilateral microinjection of l-glutamate (5, 20 and 50 mM, in 100 nl) produced a dose dependent increase in mean arterial pressure (MAP) in control (C) (16+/-5 mm Hg; 29+/-6 mm Hg; 43+/-6 mm Hg) and swim (SW) (1+/-1 mm Hg; 16+/-2 mm Hg; 25+/-3 mm Hg) groups. However, the magnitude of this response was lower in the swim group. Prazosin injection produced hypotension and tachycardia in both groups (C=-43+/-3 mm Hg/98+/-16 bpm; SW=-61+/-5 mm Hg/115+/-32 bpm). In the SW group the hypotension caused by prazosin was greater compared to C group, but the tachycardia was not different between them. After prazosin, glutamate response in RVLM was blocked in both groups as well. When glycine (10 mM or 1 M, in 100 nl) were microinjected into the RVLM of C group we observed two different effects: decrease in MAP with the lower dose and an increase in MAP with the higher dose (10 mM=-13+/-2 mm Hg; 1 M=47+/-6 mm Hg). However, after ST the hypertensive response to glycine was blunted with no alterations in the hypotensive response (10 mM=-14+/-1 mm Hg; 1 M=18+/-4 mm Hg). These findings suggest that RVLM is involved in the modulation of the sympathetic outflow to the cardiovascular system during exercise training.
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http://dx.doi.org/10.1016/j.autneu.2005.07.007DOI Listing
October 2005